CANCER INTERVENTION AND SURVEILLANCE MODELING NETWORK (CISNET)
Release Date: July 9, 2001
RFA: RFA-CA-02-010 (see reissue RFA-CA-05-018)
National Cancer Institute
Letter of Intent Receipt Date: October 9, 2001
Application Receipt Date: November 13, 2001
This RFA is a reissue of RFA-CA-99-013, which was published in NIH Guide on
August 18, 1999.
PURPOSE
The Division of Cancer Control and Population Sciences (DCCPS), National Cancer
Institute (NCI), invites applications from domestic and foreign applicants to
support collaborative research using simulation and other modeling techniques
to describe the impact of interventions (i.e., primary prevention, screening,
and treatment) in population-based settings in the United States or in non-US
settings that will shed light on US population-based trends. It is well known
that great progress in the war against cancer is possible by the complete use
and adequate delivery of existing modalities of cancer control. The primary
goals of this research are:
1) to determine the impact of cancer control interventions on observed trends
in incidence and/or mortality; and to
2) to determine if recommended interventions are having their expected
population impact by examining discrepancies between controlled cancer
intervention study results and the population experience.
Once a general understanding of the various factors influencing current trends
has been achieved, a number of secondary goals may be addressed. Applicants
may propose secondary goals of modeling the potential impact of new
interventions on future national trends, and/or determining the impact of
targeted cancer control interventions on population outcome (i.e. evaluating
optimal cancer control strategies).
In the past most models of cancer interventions have been developed to describe
hypothetical cohorts in a trial or other limited clinical settings. It is not
the purpose of this RFA to support analysis of hypothetical or trial-based
cohorts and/or cost-effectiveness analyses, but rather to support analyses
based on realistic scenarios of population impact. Projects will focus on
models describing the population impact of the observed dissemination of cancer
control interventions as well as other factors on observed national incidence
and/or mortality trends.
This second round of funding for CISNET will be limited to applications
focusing on prostate, colorectal, and lung cancers. For a summary of currently
funded CISNET projects from the first round of funding (which started in FY
2000) in breast, prostate, and colorectal cancer see
http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html.
To keep applications focused, each will be limited to a single cancer site.
The cooperative agreement mechanism calls for the development of site-specific
working groups that will: (1) facilitate comparative analyses, (2) allow
modeling groups access to a broader array of data resources and
interdisciplinary expertise and (3) provide a forum for discussions of
validation and other methodologic issues. The CISNET will allow for diversity
and originality of modeling approaches that can be compared using uniform
criteria.
The Division of Cancer Control and Population Sciences, which fulfills a
federal-level function to respond to evolving surveillance questions of
national policy relevance, helps focus research questions and act as a conduit
to national data resources necessary for parameter estimation, model
calibration, validation and population trends. An emergent property of this
collaborative agreement is progress towards a comprehensive understanding of
the determinants of cancer site-specific trends at the population level and a
better understanding of the science of modeling.
RESEARCH OBJECTIVES
Background
Modeling is the use of mathematical and statistical techniques within a logical
framework to integrate and synthesize known biological, epidemiological,
clinical, behavioral, genetic and economic information. Simulation and other
modeling techniques have been utilized to describe the impact of cancer
interventions (i.e., primary prevention, screening, and treatment) for
hypothetical cohorts or in trial and other clinical settings. The goal of this
RFA is to promote the application and extension of these models to population-
based settings in order to ascertain determinants of cancer trends. This
information is critical to the National Cancer Institute because of the
necessity of understanding: (1) if recommended interventions are having their
expected population impact, and (2) to predict the potential impact of new
interventions on national trends. These studies will often involve
extrapolation of results of controlled cancer intervention studies to estimates
of U.S. population and community effectiveness. This type of modeling
addresses issues of population-based policies and programs, and is distinct
from individual level models of risk and models of clinical decision making
used at the individual patient-physician level. An additional goal of this
concept is to advance methodology for modeling and to develop more uniform
criteria for model validation in the population setting.
The National Cancer Institute (NCI) has a longstanding need to provide answers
to critical research questions that cannot be obtained from direct observation
because of expense, ethical, or other reasons. For example, a trial is only
conducted in a limited study population under limited study conditions and
extrapolation to other settings and conditions may only be feasible through
modeling. Lead time, the time which a diagnosis is advanced through screening,
often may only be estimated through modeling because it is unethical to leave a
screen detected patient untreated until clinical symptoms develop. Prior to
the CISNET, NCI had supported a variety of small efforts in this area through
in-house work, contracts and grants. The majority of extramural efforts have
been directed at the analysis of specified cancer control interventions using a
variety of modeling approaches applied to a hypothetical cohort or in the
context of a trial or other limited settings, while the in-house work has
mainly been directed toward addressing cancer surveillance issues at the
national level. There has been growing recognition that much can be gained by
integration of these two approaches.
Models have increasingly been used in recent years to inform public health
policy decisions at the national level. In Europe, the cervical and breast
cancer screening models have been used to design, monitor and evaluate national
screening programs in several countries [1]. Models have been used in the
United States to understand the implication of dramatic changes in national
cancer statistics, such as patterns of increasing incidence related to
screening for breast and prostate cancer [2-4], improving survival due to the
dissemination of breakthrough treatment approaches in Hodgkin's Disease and
testicular cancer [5-6].
Macro-level models use estimates of standard population-based statistics (i.e.,
birth rates, incidence, stage-distribution, relative survival, and mortality
from causes other than cancer) as parameter estimates to model the life-process
in terms of birth, the development of cancer, and death from cancer or other
causes. The impact of cancer control interventions aimed at primary
prevention, screening, and treatment are estimated by changing the model
parameters. This approach has proven useful in evaluating the potential costs
and benefits of specific cancer control strategies, and exploring the impact of
these interventions on population-based cancer incidence and mortality
statistics. For example, CAN*TROL (a computer program developed by Dr. David
Eddy for cancer control planning for the World Heath Organization and adapted
for use at the NCI) [7] is a tool which has been used to examine the cost-
effectiveness of various strategies for breast cancer screening, and models of
this type are currently being used to evaluate the impact of the introduction
of adjuvant therapy on breast cancer mortality as well as the impact of changes
in modifiable risk factors on colon cancer incidence. CAN*TROL has proven to be
an effective tool for responding to policy questions from Congress and other
sources addressed to the NCI.
Macro-level models have their limitations. For example, macro-level models do
not capture individual disease history, especially the pre-clinical phase, nor
how early detection might alter that history. These dynamics are best captured
using other types of models such as microsimulation. While these modeling
efforts have been invaluable in providing insight into the cost and
effectiveness of specific intervention strategies, they are not designed to
directly address the question of how trends in screening dissemination at the
national level affect trends in cancer incidence, survival, mortality, and
cost. Recent efforts have been made to adapt these models to address
population level surveillance questions. While in the past these models have
been utilized to model hypothetical cohorts in an organized screening program,
the NCI has facilitated efforts to model opportunistic screening for multiple
cohorts reflecting the varying cancer risk of U.S. population over time. For
example, current efforts are underway to model the impact of the dissemination
of the PSA screening test in the US population on prostate cancer incidence and
mortality [8]. Validating against current population trends can provide
further clues concerning lead-time, over diagnosis, and the timing and size of
potential mortality declines.
In conjunction with the development of these models, there have been various
methodologic spin-offs that have broad uses in a variety of modeling settings.
For example, NCI researchers, in collaboration with extramural researchers,
have investigated the issue of obtaining variability of estimates from
microsimulations [9], estimation techniques have been developed for the
incidence of pre-clinical prostate cancer from autopsy prevalence data [10],
and issues related to model validation have been explored.
OBJECTIVES AND SCOPE
The objective of this RFA is to enhance research on the development and use of
models to evaluate the impact of cancer control interventions on population
level statistics. Funding consists of two rounds in FY2000 and FY2002. In
FY2000 applications were restricted to breast, prostate and colorectal cancer.
These are three major cancer control sites where there is substantial modeling
experience and, for the most part, interest in the population impact of all
three modalities of cancer control (screening, treatment, and primary
prevention). Seven breast applications were funded, as well as one apiece in
prostate and colorectal cancer. For the list of currently funded projects and
their abstracts see: http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html. Also
listed on the web site will be schedules for phone conference calls to discuss
the existing CISNET program/work, the scope of the current RFA, and answer
questions by potential applicants. There will probably be one conference call
per cancer site (i.e. prostate, colorectal and lung cancer). Summaries of the
calls and/or tapes will be available for those unable to participate directly.
Based on our funding results from the first round, the second round of funding
will be limited to prostate, colorectal, and lung cancer. To keep applications
focused, each proposal will be limited to a single cancer site. New
investigators will be expected to join in the ongoing collaborative activities
already underway.
All of the proposals must include a central focus on the modeling the impact of
cancer control interventions and other factors on observed national trends in
incidence and/or mortality. Examples of this type of research include:
(A) Model of the population impact of the introduction of new therapies using
estimates of the impact of these therapies in controlled settings and
population dissemination patterns (e.g., a model of the impact of adjuvant
chemotherapy on colon cancer mortality starting in 1989).
(B) Model of the impact of interventions aimed at changing modifiable risk
factors on population trends in incidence and/or mortality (e.g. model the
impact of US and regional smoking cessation and smoking reduction patterns on
lung cancer incidence and/or mortality).
(C) Model of the impact of screening on population incidence and/or mortality
patterns using a model of disease natural history, the population dissemination
of screening, and the operating characteristics of these screening modalities
(e.g. what are the relative roles of screening (i.e., early detection), and
polyp removal (i.e. prevention) on colorectal cancer incidence trends).
(D) Use discrepancies between modeled and observed population trends to study
the community effectiveness of interventions (e.g. study discrepancies between
model predictions and observed data to better understand how community
screening practices differ from trials. The sensitivity of screening test may
be better than in a trial setting because of improved technology developed
since the trial or worse because of less expert application of technology
compared to the trial setting).
In addition to a central focus on observed trends in incidence and/or
mortality, applications may also include applications of models that:
(1) Predict the impact of new interventions on national trends (e.g., model the
potential impact of spiral CT screening on lung cancer mortality; model the
impact of new tobacco products on lung cancer incidence and/or mortality).
(2) Determine the impact of targeted cancer control interventions on population
outcome (e.g., model the population impact of targeting different age groups,
risk groups, adherence to initial versus repeat screening guidelines; model the
impact of programs to encourage smoking reduction versus smoking cessation on
lung cancer incidence and/or mortality).
The purpose of these efforts is to model the impact of the observed
dissemination of cancer control interventions in the population, rather than
using observed population trends to postulate new risk factors. However, these
models can include components which model the impact of population changes in
both modifiable and non-modifiable risk factors. Models which include the
impact of multiple interventions simultaneously, e.g., the synergistic effects
of screening and treatment, are desirable. Models can be of the entire US
population, a region of the country, or some specific identified population
where unique data exists on the implementation of an intervention, or in a
subpopulation of specific interest (e.g., rural poor). Models can be developed
for non-US populations, but should be justified based on their applicability to
understanding US cancer trends. Models can focus on one aspect of a disease
(e.g., polyp development and removal), although justification must be given as
to how one part of the disease process can be modeled separately, and how this
model can be integrated into the complete disease picture. It is not the
purpose of this RFA to support analysis of hypothetical or trial-based cohorts
and/or cost effectiveness analysis, but rather to support analysis based on
realistic scenarios of population impact.
Applications should demonstrate modeling capability, and propose a specific
research plan. However, applicants should be flexible enough to accommodate
further refinement and integration with other efforts.
SPECIAL REQUIREMENTS
Research Plan
Applications in response to the RFA must address the following areas:
Specific Aims/Background and Significance - The application must clearly state
the surveillance research questions which this application is designed to
address and the importance of these issues for cancer control in the US. If
the proposal includes the modeling of trends outside of the US, justification
must be given as to what special insights this will give in understanding of US
trends, how these results will be related to US trends, and why the same models
could not be applied directly to US data. All applications must include as a
primary objective modeling of the impact of cancer control interventions and
other factors on observed national trends in incidence and/or mortality.
Applicants should discuss plans to develop, calibrate, and validate these
models. A well-calibrated and validated model of observed trends will allow
possible extensions to secondary objectives, which can include projecting the
impact of new interventions on future trends, as well as designing optimal
cancer control strategies.
Preliminary Studies/Research Design and Methods - Since the application of
models of cancer interventions to population based trends is a relatively new
area, applicants should describe in detail their approach to adaptation of
current models, and demonstrate an understanding of the problems inherent in
working with population based data. The application must describe the nature
and characteristics of the model to be employed. Is this a new or existing
model? How will the model be adapted to address population-based surveillance
questions? The application must describe the proposed data resources for model
development and validation, a description of areas of potential collaboration
with other grantees in this cooperative agreement, strategies for identifying
and characterizing differences between modeled and observed population trends,
and the overall approach towards developing a comprehensive understanding of
the determinants of cancer site-specific trends at the population level.
Contractual Arrangements – The application should describe contractual
arrangement necessary for acquisition and/or consolidation of data necessary
for parameter estimation. Any other contractual arrangements should also be
described.
In addition, investigators should state their willingness to participate in
joint meetings, to share methods and data resources, and to embark on
collaborative efforts to decide overall research direction. For example, to
allow for easier model comparisons, applicants may be asked to cooperate on a
standardized “base case” where common model inputs (e.g. dissemination of
screening in the US population) and outputs would be mutually agreed upon by
cancer site working group participants. Investigators will be asked to post
project descriptions and pre-submission publications for comment and review by
the cooperative group.
Budget
First year costs may include funds for such activities as model development,
model validation, acquisition of data for parameter estimation, methods
development, and/or use or purchase of high-speed computer systems. Activities
may involve the acquisition and/or consolidation of data necessary for
parameter estimation, model calibration, or validation, and subcontracts may be
employed if necessary to make these efforts possible. For purposes of
budgeting, funds should be requested for up to three persons to travel to two
cancer-site specific working group meetings, and one methodology meeting per
year for each of the four years of the award. It is anticipated that an annual
meeting will be a joint meeting with representatives from all four cancer
sites, and will include the methodology meeting as well. The mid-year meetings
will usually be separate cancer site-specific meetings
If a PI, or an institution wishes to submit several applications which share a
common structure (e.g., models for breast and prostate cancer which share a
similar computing framework), funds to develop or enhance that common structure
should be included separately in each application, and duplication of funding
activities will be negotiated at the time of award. Likewise, travel funds for
each application should be considered separately, and overlapping funding will
be negotiated at the time of award. Finally, a submission from one institution
may contain subcontracts for consultation from another institution, which may
be unnecessary if both institutions are funded under CISNET. Areas of
potential duplication of funds across multiple applications should be clearly
identified.
Terms and Conditions of Award
The following terms and conditions will be incorporated into the award
statement and provided to the Principal Investigator(s) as well as the
institutional official at the time of award.
Under this cooperative agreement, a partnership will exist between the
recipient of the award and the NCI. These special Terms of Award are in
addition to, and not in lieu of, otherwise applicable OMB administrative
guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, and
other HHS, and NIH Grant Administration policy statements.
The administrative and funding instrument used for this program is a
cooperative agreement (U01), an "assistance" mechanism (rather than an
"acquisition" mechanism) in which substantial NCI scientific and/or
programmatic involvement with the awardee is anticipated during performance of
the activity. Under the cooperative agreement, the NCI purpose is to support
and/or stimulate the recipient's activity by involvement in and otherwise
working jointly with the award recipient in a partner role, but it is not to
assume direction, prime responsibility, or a dominant role in the activity.
Consistent with this concept, the dominant role and prime responsibility for
the activity resides with the awardee(s) for the project as a whole, although
specific tasks and activities in carrying out the studies will be shared among
the awardees and the NCI Scientific Staff.
1. Definitions:
AWARDEES: Institutions receiving cooperative agreements through this RFA.
NCI PROGRAM DIRECTOR: A scientist administrator from the NCI extramural staff,
the Program Director, will not only provide normal stewardship for the U01
grants awarded under this RFA, but will also be involved in the scientific
coordination and collaboration within the Network and will coordinate
interaction between the research groups.
PRINCIPAL INVESTIGATOR (PI): The investigator who is designated by the
applicant organization to direct the project to be supported by the U01 grant.
The PI will assume the responsibility and accountability to the applicant
organization officials and to the NCI for the performance and proper conduct of
the research supported by the U01 mechanism. Each institution may have more
than one CISNET PI, and a single person may be the PI for applications for more
than one cancer site.
NCI SCIENTIFIC COORDINATORS: Scientists from the NCI extramural staff
designated by the Program Director to coordinate the activities for one of the
four cancer sites and the methodology working group. NCI scientific
coordinators will have substantial scientific involvement with the working
groups and will help refine research questions.
NCI SCIENTIFIC STAFF: Scientific staff from NCI's extramural and intramural
programs called upon to provide their expertise to the CISNET efforts.
EXTRAMURAL SCIENTIFIC INVESTIGATORS: Scientific staff named in the application
from the participating institutions and their subcontractors.
CANCER-SITE WORKING GROUPS: There will be four cancer site specific working
groups (breast, prostate, colorectal, and lung cancer). Voting members of each
working groups will be the PI's of each site specific grant project, and the
NCI Scientific Coordinator. Other project and NCI Scientific Staff will attend
at the discretion of the voting members. The co-chairs of the working groups
will be the NCI Scientific Coordinator and one of the PI's (chosen by mutual
consent of the PI's for that cancer site). Other subcommittees will be formed
by the working groups as needed.
METHODOLOGY WORKING GROUP: A group comprised of interested methodologists among
the extramural scientific investigators and NCI Scientific Staff. The chairs
of the methodology working groups will be one Extramural Scientific
Investigator (chosen by mutual consent of the Extramural Scientific
Investigators on the Methodology Working Group) and an NCI Scientific
Coordinator designated by the NCI Program Director. Other subcommittees will be
formed by the working group as needed.
STEERING COMMITTEE: A committee consisting of the five non-NCI chairs of the
Working groups (breast, prostate, colorectal, lung, and methodology), the NCI
Program Director, and one NCI Scientific Coordinator as designated by the NCI
Program Director. The Chair of the Steering Committee will be one of the PI's
as selected by the Steering Committee. The Steering Committee can admit
additional non-federal members as they deem necessary. The Steering Committee
will provide overall direction for the CISNET project and provide oversight to
procedures and policies.
2. Awardee Rights and Responsibilities
The award recipients must join the NCI CISNET project for the purpose of
planning, developing, and conducting collaborative projects to address high
priority surveillance research objectives. Within this framework, awardees
have primary authorities and responsibilities to define objectives and
approaches, and to plan, conduct, analyze, and publish results,
interpretations, and conclusions of their studies.
Awardees will be required to attend working group meetings and are obligated to
adhere to joint decisions for publication and research direction decided on by
the Steering Committee and the Working Groups.
Awardees will be expected to share information about model structure and
assumptions at working group meetings, as well as strategies and data resources
for parameter estimation.
Awardees will be expected to engage in efforts coordinated by the Working
Groups for calibration, validation, and comparison of model results.
Awardees will retain custody of and have primary rights to the models and model
results developed under these awards, subject to Government rights of access
consistent with current HHS, PHS, and NIH policies.
3. NCI Staff Responsibilities
The NCI Program Director and his designees will have substantial scientific-
programmatic involvement during conduct of this activity, through technical
assistance, advice and coordination above and beyond normal program stewardship
for grants.
The NCI Program Director will serve as a member of the Steering Committee.
The NCI Program Director will designate an NCI Scientific Coordinator for each
cancer site and for the methodology group who will serve as a co-chair of the
Working Groups.
The NCI Scientific Coordinators will provide information about a wide range of
data resources which will be used for parameter estimation and population
trends, and will serve as a conduit to the potential utility and access to
these resources. In addition, the NCI Scientific Coordinators will call upon
other NCI Scientific Staff to provide advice on specific scientific and
technical issues as needed.
The NCI reserves the right to reduce the budget, withhold support, or suspend,
terminate or curtail a study or an award in the event of substantial lack of
collaborative participation, failure to make satisfactory progress in
fulfilling the stated goals of the project, refusal to carry out the
recommendations of the Working Groups or the Steering Committee, or substantial
failure to comply with the terms of award.
4. Collaborative Responsibilities
A. Steering Committee
The Steering Committee will:
Be the ultimate decision making body for CISNET, unless a disagreement is
brought to arbitration.
Review, approve, and provide comments on the written reports of the Cancer
Site-Specific Working Groups. This approval process should ensure that the
proposed activities are consistent with the objectives and scope as specified
in the RFA.
Review, approve, comment on, and provide directives for implementation based on
the written recommendations from the Methodology Working Group.
Set publication procedures and policies.
Coordinate communication between the Working Groups.
Meet at least twice a year, and schedule additional meetings and conference
calls as needed.
B. Working Groups
Meet at least twice a year.
Refine research questions that are consistent with high priority surveillance
research needs.
Identify key potential determinants and confounders of population based trends,
and to identify useful data resources to inform these models.
Collaborate to identify and select common data resources for conducting
calibration and independent model validation.
Consider the development of common modules that supply intermediate inputs to
the central simulation models (e.g., screening histories supplied by a
dissemination module, survival improvements in a screening model supplied by a
treatment dissemination module).
Consider the use of common input data for dissemination, costs, and other
parameters based on the best available national estimates.
Facilitate comparative analyses which will improve the credibility of
individual models.
Evolve into an expert knowledge base to provide technical advise on policy
relevant surveillance questions.
Will provide written reports to the Steering Committee after each Working Group
Meeting summarizing research priorities, directions, and method of
implementation.
Responsibilities of the chairs of the Working Groups will be to:
Convene working meetings.
Set meeting agendas.
Coordinate communication within the Working Group,
Set (in consultation with the working group) the publication agenda and
schedule.
The PI Co-Chair of the Working Group will serve as a voting member of the
Steering Committee, and will represent their Working Group to the Steering
Committee.
C. The Methodology Working Group will:
Meet once a year, mainly for the purpose of scientific presentation and
exchange of ideas, and to coordinate research plans where necessary.
Provide a forum for the discussion of methods development associated with the
application of microsimulation and other models to population-based questions.
At the discretion of the group, provide written recommendations to the steering
committee for common methodologic approaches and validation strategies and
development of common model components.
5. Arbitration
Any disagreement that may arise on scientific/programmatic matters (within the
scope of the award), between award recipients and the NCI may be brought to
arbitration. An arbitration panel will be composed of three members; one
selected by the recipient group, a second member selected by the NCI, and the
third member selected by the two prior selected members. This special
arbitration procedure in no way affects the awardee's right to appeal an
adverse action that is otherwise appealable in accordance with the PHS
regulations at 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16.
MECHANISM OF SUPPORT
The administrative and funding instrument to be used for this program will be a
cooperative agreement (U01), an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH scientific and/or
programmatic involvement with the awardee is anticipated during performance of
the activity. Under the cooperative agreement, the NIH purpose is to support
and/or stimulate the recipient's activity by involvement in and otherwise
working jointly with the award recipient in a partner role, but it is not to
assume direction, prime responsibility, or a dominant role in the activity.
Details of the responsibilities, relationships and governance of the study to
be funded under cooperative agreement(s) are discussed later in this document
under the section "Terms and Conditions of Award".
The total project period for applications submitted in response to the present
RFA may not exceed four years. Awards and level of support depend on receipt
of a sufficient number of applications of high scientific merit. The
anticipated award date is July 2002.
FUNDS AVAILABLE
The NCI intends to commit approximately $1,250,000 in total costs (direct and
Facilities and Administrative (F&A) costs) in FY 2002 to fund 4 to 6 new grants
in response to this RFA. An applicant may request a project period of up to
four years. It is anticipated that the award for each application for modeling
of a single cancer site will be between $75,000 to a maximum of $250,000 total
cost for the first year. It is anticipated that several modeling centers will
submit applications for more than one cancer site. Each individual application
must be limited to one cancer site. Because the nature and scope of the
research proposed may vary, it is anticipated that the size of each award will
also vary. Applications on the lower end of range (e.g., $75,000 - $125,000)
are encouraged for smaller more focused efforts, while those at the higher end
of the range ($125,000-$250,000) are for more comprehensive population-based
applications which consider the entire spectrum of the disease process and/or
model multiple interventions simultaneously. Although the financial plans of
the NCI provide support for this program, awards pursuant to this RFA are
contingent upon the availability of funds and the receipt of a sufficient
number of applications of outstanding scientific and technical merit.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign for-profit and non-profit
organizations, public and private, such as universities, colleges, medical
centers, units of State and Local governments, and eligible agencies of the
Federal Government. Applications from minority individuals, women, and persons
with disabilities, are encouraged to apply.
Each Principal Investigator (PI) is limited to only one application per cancer
site, and thus up to three applications are possible by one PI. If a PI, or an
institution, is submitting several applications that share a common structure
(e.g., models for lung and prostate cancer which share a similar computing
framework), funds to develop or enhance that common structure should be
included separately in each application, and overlapping funding of activities
will be considered at the time of award (see Special Requirements - Budget).
INQUIRIES
Written and telephone inquiries concerning this RFA are encouraged. The
opportunity to clarify any issues or questions from potential applicants is
welcome. The NCI will be holding a series of phone conference calls (probably
one for each cancer site) for applicants to hear more about the existing CISNET
work, and to discuss the scope of potential applications. For more information
about the schedule for these calls see
http://www-dccps.ims.nci.nih.gov/SRAB/cisnet.html. Summaries of the calls
and/or tapes will be available for those unable to participate directly.
Direct inquiries regarding programmatic issues to:
Dr. Eric Feuer
Division of Cancer Control and Population Sciences
National Cancer Institute
6116 Executive Boulevard, Room 5041, MSC 8317
Bethesda, MD 20892-8317
Telephone: (301) 496-5029
Fax: (301) 480-2046
Email: rf41u@nih.gov
Direct inquiries regarding review issues to:
Ms. Toby Friedberg
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd., Room 8109, MSC 8329
Bethesda, MD 20892-8329
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-3428
Fax: (301) 402-0275
Email: tf12w@nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Crystal Wolfrey
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
Bethesda, MD 20892-7510
Telephone: (301) 496-8634
Fax: (301) 496-8601
Email: crystal.wolfrey@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit, by October 9, 2001 a letter of
intent that includes a descriptive title of the proposed research, name,
address, and telephone number of the Principal Investigator, identities of
other key personnel and participating institutions, and number and title of the
RFA in response to which the application may be submitted.
Although a letter of intent is not required, is not binding, and does not enter
into the review of subsequent applications, the information allows NCI staff to
estimate the potential review workload and to plan the review.
The Letter of Intent is to be sent to the program staff listed under INQUIRES
by the letter of intent receipt date listed in the heading of this RFA.
SCHEDULE
Letter of Intent Receipt Date: October 9, 2001
Application Receipt Date: November 13, 2001
Review by NCAB Advisory Board: May 2002
Earliest Anticipated Start Date: July 2002
APPLICATION PROCEDURES
The research grant application form PHS 398 is to be used in applying for these
grants. All instructions apply unless otherwise noted. Applications kits are
available at most institutional offices of sponsored research and may be
obtained from the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD
20892-7910, telephone 301/710-0267, E-mail: grantsinfo@nih.gov. For those
applicants with internet access, the 398 kit may be found at
https://grants.nih.gov/grants/funding/phs398/phs398.html
The RFA label available in the PHS 398 application form must be affixed to the
bottom of the face page of the application. Type the RFA number on the label.
Failure to use this label could result in delayed processing of the application
such that it may not reach the review committee in time for review. In
addition, the RFA title and number must be typed on line 2 of the face page of
the application form and the YES box must be marked.
The sample RFA label available at:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to
allow for this change. Please note this is in pdf format.
Submit a signed, typewritten original of the application, including the
Checklist, and three signed photocopies, in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive
Room 1040 - MSC 7710
Bethesda, MD 20892-7710
(20817 for express service)
At the time of submission, two additional copies of the application must also
be sent to:
Ms. Toby Friedberg
Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd., Room 8109, MSC-8329
Rockville, MD 20852 (express courier)
Bethesda, MD 20892-8329
Applications must be received by November 13, 2001. If an application is
received after that date, it will be returned to the applicant without review.
The Center for Scientific Review (CSR) will not accept any application in
response to this announcement that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending application.
The CSR will not accept any application that is essentially the same as one
already reviewed. This does not preclude the submission of a substantial
revision of an application already reviewed, but such an application must
include an introduction addressing the previous critique.
REVIEW CONSIDERATIONS
Applicants are encouraged to submit and describe their own ideas about how best
to meet the general research goals outlined in this RFA, and are expected to
address issues identified under SPECIAL REQUIREMENTS of the RFA.
Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness by the National Cancer Institute. Incomplete and/or non-
responsive applications will be returned to the applicant without further
consideration.
Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the Division of Extramural Activities of the National Cancer Institute in
accordance with the review criteria stated below. As part of the initial merit
review, a process will be used by the initial review group in which
applications receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit, generally the
top half of the applications under review, will be discussed assigned a
priority score, and receive a second level review by the National Cancer
Advisory Board.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. The
reviewers will comment on the following aspects of the application in their
written critiques in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals. Each of these
criteria will be addressed and considered by the reviewers in assigning the
overall score weighting them as appropriate for each application.
1. Significance. Does this study address an important population-based
surveillance problem? If the aims of the application are achieved, how will
surveillance research and cancer control be advanced? What will be the
potential effect of these studies on policy of health care practices that could
ultimately improve the health of the American public? Does this application
address realistic strategies and issues, rather than proposed optimal
strategies that may have no real chance of ever being implemented in the
population.
2. Approach. Are the nature and characteristics of the model to be employed
adequate? How will the model be adapted to address population-based
surveillance questions? Does the applicant have a plan for demonstrating a
general understanding of the various factors influencing observed trends before
investigating secondary goals of future trends and optimal cancer controls
strategies? What are the strategies for identifying and characterizing
differences between modeled and observed population trends, and general
approach towards developing a comprehensive understanding of the determinants
of cancer site-specific trends at the population level? Are the conceptual
framework, design, methods, and analyses adequately developed, well integrated,
and appropriate to the aims of the project? Does the applicant acknowledge
potential problem areas and consider alternative tactics?
3. Innovation. Does the project employ novel concepts, approaches or method?
Are the aims original and innovative? Does the application describe in detail
their approach to adaptation of current models for population modeling, and
demonstrate an understanding of the problems inherent in working with
population based data.
4. Investigator. Is the investigator appropriately trained and well suited to
carry out this work? Do the investigators have extensive modeling experience?
Is the work proposed appropriate to the experience level of the principal
investigator and other researchers (if any)? Do the investigators comprise an
interdisciplinary team that is adequate to carry out the proposed work?
5. Environment. Does the scientific environment in which the work will be
done contribute to the probability of success? Is modeling activities an
established element of the research environment? Do the proposed modeling
efforts take advantage of unique features of the scientific environment or
employ useful collaborative arrangements? Is there evidence of institutional
support?
6. Collaboration. Do the investigators state their willingness to participate
in joint meetings, be willing to share methods and data resources, and to
embark on collaborative efforts to decide overall research direction? Do the
investigators have a documented history of engaging in collaborative modeling
research with: (a) colleagues at their own institution, (b) modeling groups at
other institutions, (c) providers of primary data sources, and (d) policy
oriented organizations or agencies? Documentation could include letters of
support from prior collaborations.
7. Relevance. Does the application have as its primary goal modeling observed
trends in incidence and/or mortality as a function of cancer control
interventions and other factors? If the application includes secondary goals
concerning modeling of future trends and/or optimal cancer control strategies,
do these modeling efforts reflect realistic scenarios, which could be achieved
in actual population settings?
The initial review group will also examine: the appropriateness of proposed
project budget and duration; the adequacy of plans to include both genders,
minorities and their subgroups, and children as appropriate for the scientific
goals of the research and plans for the recruitment and retention of subjects;
the provisions for the protection of human and animal subjects; and the safety
of the research environment.
AWARD CRITERIA
Applications recommended by the National Cancer Advisory Board will be
considered for award based upon (a) scientific and technical merit; (b) program
balance, including in this instance, a reasonable representation of projects
across all three cancer sites, and sufficient compatibility of features to make
a successful collaborative program a reasonable likelihood; and (c)
availability of funds.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and their
sub- populations must be included in all NIH-supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research. This policy results from the NIH Revitalization Act of 1993 (Section
492B of Public Law 103-43).
All investigators proposing research involving human subjects should read the
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," published in the NIH Guide for Grants and Contracts on
August 2, 2000
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); a complete
copy of the updated Guidelines is available at
https://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The
revisions relate to NIH defined Phase III clinical trials and require: a) all
applications or proposals and/or protocols to provide a description of plans to
conduct analyses, as appropriate, to address differences by sex/gender and/or
racial/ethnic groups, including subgroups, if applicable; and b) all
investigators to report accrual, and to conduct and report analyses, as
appropriate, by sex/gender and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS.
It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are clear and compelling scientific and ethical reasons not
to include them. This policy applies to all initial (Type 1) applications
submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL
address: https://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators may also obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS
All investigators proposing research involving human subjects should read the
NIH policy on education in the protection of human research participants now
required for all investigators, which is published in the NIH Guide for Grants
and Contracts, June 5, 2000 (Revised August 25, 2000), available at the
following URL address:
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
A continuing education program in the protection of human
participants in research is now available online at http://cme.nci.nih.gov/.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT
The Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a project
that is supported in whole or in part with Federal funds and (2) cited publicly
and officially by a Federal agency in support of an action that has the force
and effect of law (i.e., a regulation) may be accessed through FOIA. It is
important for applicants to understand the basic scope of this amendment. NIH
has provided guidance at
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants
may wish to place data collected under this RFA in a public archive, which can
provide protections for the data and manage the distribution for an indefinite
period of time. If so, the application should include a description of the
archiving plan in the study design and include information about this in the
budget justification section of the application. In addition, applicants should
think about how to structure informed consent statements and other human
subjects procedures given the potential for wider use of data collected under
this award.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained within
specified page limitations. Unless otherwise specified in an NIH solicitation,
Internet addresses (URLs) should not be used to provide information necessary
to the review because reviewers are under no obligation to view the Internet
sites. Reviewers are cautioned that their anonymity may be compromised when
they directly access an Internet site.
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This RFA, the Cancer Intervention
Surveillance Modeling Network (CISNET), is related to the priority area of
cancer surveillance and data systems. Potential applicants may obtain a copy
of "Healthy People 2010" at http://www.health.gov/healthypeople/.
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.399, Awards are made under authorization of Sections 301 and 405 of the
Public Health Service Act as amended (42 USC 241 and 284) and administered
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74
and 92. This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency review.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and promote the non-use of all tobacco products. In addition, Public
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care, or early childhood
development services are provided to children. This is consistent with the PHS
mission to protect and advance the physical and mental health of the American
people.
REFERENCES
1. van den Akker-van Marle E, de Koning H, Boer R, van der Maas P. Reduction
in breast cancer mortality due to the introduction of mass screening in the
Netherlands: comparison with the United Kingdom. J Med Screen 1999;6:30-34.
2. Feuer, E.J., Wun, L.M. "How Much of the Recent Rise in Breast Cancer
Incidence Can be Explained by Increases in Mammography Utilization: A Dynamic
Population Approach," American Journal of Epidemiology, 1992; 136, 1423-1436.
3. Wun, L.M. Feuer, E.J., Miller, B.A. "Are Increases in Mammographic
Screening Still a Valid Explanation for Trends in Breast Cancer Incidence in
the United States?" Cancer Causes and Control, 1995; 6, 135-144.
4. Legler, J.M., Feuer, E.J., Potosky, A.L., Merrill, R.M., Kramer, B.S.,
"The Role of Prostate-Specific Antigen Testing Patterns in the Recent Prostate
Cancer Incidence Decline," Cancer Causes and Control, 1998; 9, 519-527.
5. Feuer, E.J., Kessler, L.G., Triolo, H.E., Baker, S.G., Green, D.T. "The
Impact of Breakthrough Clinical Trials on Survival in Population Based Tumor
Registries," Journal of Clinical Epidemiology, 1991; 44, 141-153.
6. Weller, E.A., Feuer, E.J., Frey, C.M., Wesley, M.N., "Parametric Relative
Survival Modeling Using Generalized Linear Models with Application to
Hodgkin's Lymphoma," Applied Statistics, 1999; 48, 79-89.
7. Levin DL, Gail MH, Kessler LG, Eddy DM, "A Model for Projecting Cancer
Incidence and Mortality in the Presence of Prevention, Screening, and
Treatment Programs," NCI Monographs, 2:83-93, 1986.
8. Etzioni, R, Legler, JM, Feuer, EJ, Merrill, RM, Cronin, KA, Hankey, BF,
"Cancer Surveillance Series: Interpreting Trends in Prostate Cancer - Part
III: Quantifying the Link Between Population Prostate-Specific Antigen Testing
and Recent Declines in Prostate Cancer Mortality," JNCI , 91: 1033-1039, 1999.
9. Cronin KA, Legler, JM, Etzioni RD, "Assessing Uncertainty in
Microsimulation Modeling with Application to Cancer Screening Applications,"
Statistics in Medicine, 1998; 17:2509-23.
10. Etzioni, R., Cha, R, Feuer, E.J., Davidov, O. "Asymptomatic Incidence and
Duration in Prostate Cancer,." American Journal of Epidemiology, 1998; 148,
775-785.